Flight behaviour in humans is intensified by a candidate genetic risk factor for panic disorder: evidence from a translational model of fear and anxiety

Perkins, Adam; Ettinger, Ulrich; Williams, Steven; Reuter, Martin; Hennig, Juergen; Corr, Philip J.

doi:10.1038/mp.2010.2

Cited by 12 publications

(14 citation statements)

References 12 publications

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“…For example, in the human joystick-operated runway task (JORT; analogue to the mouse defense battery test), the participant controls the speed of a moving cursor that is trapped between two threat stimuli. This task has been used to study anxiety (elicited by threats that may require approach and thus cause goal conflict) and fear (elicited by threats that need to be avoided), including their genetic correlates and modulation by anxiolytics and antidepressants (Perkins et al, 2009; Perkins et al, 2011). …”

Section: Human Paradigmsmentioning

confidence: 99%

Animal to human translational paradigms relevant for approach avoidance conflict decision making

Kirlić

Young

Aupperle

2017

Behaviour Research and Therapy

102

112

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Avoidance behavior in clinical anxiety disorders is often a decision made in response to approach-avoidance conflict, resulting in a sacrifice of potential rewards to avoid potential negative affective consequences. Animal research has a long history of relying on paradigms related to approach-avoidance conflict to model anxiety-relevant behavior. This approach includes punishment-based conflict, exploratory, and social interaction tasks. There has been a recent surge of interest in the translation of paradigms from animal to human, in efforts to increase generalization of findings and support the development of more effective mental health treatments. This article briefly reviews animal tests related to approach-avoidance conflict and results from lesion and pharmacologic studies utilizing these tests. We then provide a description of translational human paradigms that have been developed to tap into related constructs, summarizing behavioral and neuroimaging findings. Similarities and differences in findings from analogous animal and human paradigms are discussed. Lastly, we highlight opportunities for future research and paradigm development that will support the clinical utility of this translational work.

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Section: Human Paradigmsmentioning

confidence: 99%

Animal to human translational paradigms relevant for approach avoidance conflict decision making

Kirlić

Young

Aupperle

2017

Behaviour Research and Therapy

102

112

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“…97, 98 An association of 5-HT biosynthetic enzyme TPH-2 and 5-HT receptor subtypes R1 and R2 with PD has also been reported. 99, 100, 101 The 5-HT system is of interest given its role in the regulation of panic-like behaviors. 102 Importantly, evidence of chemosensory serotonergic neurons in the medullary raphe (see section ‘Acid chemosensory serotonergic neurons in the medullary raphe nucleus') underscores the role of the 5-HT system in translation of pH fluctuations to panic-relevant ventilatory responses.…”

Section: Acidosis An Interoceptive Trigger In Panic: Evidence For Rementioning

confidence: 99%

Acid–base dysregulation and chemosensory mechanisms in panic disorder: a translational update

2015

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Panic disorder (PD), a complex anxiety disorder characterized by recurrent panic attacks, represents a poorly understood psychiatric condition which is associated with significant morbidity and an increased risk of suicide attempts and completed suicide. Recently however, neuroimaging and panic provocation challenge studies have provided insights into the pathoetiology of panic phenomena and have begun to elucidate potential neural mechanisms that may underlie panic attacks. In this regard, accumulating evidence suggests that acidosis may be a contributing factor in induction of panic. Challenge studies in patients with PD reveal that panic attacks may be reliably provoked by agents that lead to acid–base dysbalance such as CO2 inhalation and sodium lactate infusion. Chemosensory mechanisms that translate pH into panic-relevant fear, autonomic, and respiratory responses are therefore of high relevance to the understanding of panic pathophysiology. Herein, we provide a current update on clinical and preclinical studies supporting how acid–base imbalance and diverse chemosensory mechanisms may be associated with PD and discuss future implications of these findings.

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“…Further evidence comes from two experimental studies (25,26) using a human version of the mouse defense test battery, a procedure that assesses behavioral indexes of anxiety and fear/panic separately and that has been pharmacologically validated (27). In the task designed to represent a potential threat, healthy volunteers use a force-sensing joystick to control the speed of a green dot cursor that moves within a vertical alley on a video screen, when it is trapped between two immobile red dot threat stimuli.…”

Section: -Ht and Panicmentioning

confidence: 99%

“…In contrast, the same drug did not change the performance of the escape task, hypothetically related to fear. In the second study (26), the escape task was measured in participants who differed in genetic risk for PD. The genetic risk factor used was the C allele of the 102T/C single-nucleotide polymorphism (rs6313) within the serotonin 2A receptor gene (HTR2A) on chromosome 13q14.2.…”

Section: -Ht and Panicmentioning

confidence: 99%

New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

Graeff

2012

Braz J Med Biol Res

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Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

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Flight behaviour in humans is intensified by a candidate genetic risk factor for panic disorder: evidence from a translational model of fear and anxiety

Cited by 12 publications

References 12 publications

Animal to human translational paradigms relevant for approach avoidance conflict decision making

Animal to human translational paradigms relevant for approach avoidance conflict decision making

Acid–base dysregulation and chemosensory mechanisms in panic disorder: a translational update

New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

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